The current standard of care for use of thrombolytic in clinical treatment of acute peripheral arterial occlusion (aPAO) is intrathrombus administration of tissue plasminogen activator (t-PA). In approximately 20% of patients administered t-PA via intrathrombus delivery, dissolution of clot is heralded by temporary worsening of the lower leg ischemia prior to improvement. This temporary worsening corresponds to fragmentation of the clot and showering of emboli into distal circulation. Over the next 6-12 hours, the systemic activity of t-PA is known to slowly dissolve these clots, after which symptoms of worsening ischemia generally abate. The condition of the patient subsequently improves slowly to ameliorate the aPAO symptoms that represent native artery or graft occlusion.
One of the safety advantages of a thrombolytic agent such as plasmin is its ability to be neutralized rapidly in the blood by circulating inhibitors. However, there is evidence to suggest that the flow dynamics of a treatment zone can be such that plasmin may escape into the bloodstream prior to contacting its fibrin substrate on the clot and also that blood along with its contained inhibitors can enter the treatment zone during plasmin application and interfere with thrombolysis by inactivating the plasmin.
A need remains for thrombolytic agent delivery devices, systems, and methods that also provide for effective occlusion of a vessel or graft distal and/or proximal to an occlusion.